HUVEC-EVs通过JAK2/STAT3通路促进乳腺癌细胞增殖和迁移

目的: 探讨人脐静脉内皮细胞来源胞外囊泡(human umbilical vein endothelial cell-derived extracellular vesicles, HUVEC-EVs)对乳腺癌细胞增殖和迁移的影响及其作用机制。方法: 采用不同浓度(0、10、20、40 μg/mL) HUVEC-EVs分别处理乳腺癌MDA-MB-231和MCF-7细胞24 h，通过MTT实验和平板克隆形成实验检测乳腺癌细胞增殖能力，Transwell实验检测乳腺癌细胞迁移和侵袭能力，划痕实验检测乳腺癌细胞迁移能力，蛋白质印迹实验检测乳腺癌细胞JAK2/STAT3信号通路相关蛋白的表达。结果： 与0 μg/mL HUVEC-EVs空白对照组相比，10、20、40 μg/mL HUVEC-EVs处理组乳腺癌MDA-MB-231和MCF-7细胞增殖能力明显提高(P<0.05)，平板克隆形成能力、迁移和侵袭能力也明显增强(P<0.05)，总JAK2、STAT3蛋白无明显变化(P>0.05)，而p-JAK2、p-STAT3蛋白表达升高(P<0.05)。结论： HUVEC-EVs可能通过JAK2/STAT3信号通路的磷酸化促进乳腺癌细胞增殖及迁移。

HUVEC-EVs promote breast cancer cell proliferation and migration through activation of the JAK2/STAT3 pathway

Objective: To investigate the effect of human umbilical vein endothelial cell-derived extracellular vesicles (HUVEC-EVs) on proliferation and migration of human breast cancer cells and its potential mechanisms.  Methods: Different concentrations of HUVEC-EVs (0, 10, 20 and 40 μg/mL) were used to treat MDA-MB-231 and MCF-7 breast cancer cells for 24 h, the proliferation was detected by MTT assay and plate clone formation assay. Transwell assay was used to detect the migration and invasion, scratch wound assay was used to detect the migration and Western blotting was to detect related protein expression of JAK2/STAT3 signaling pathway. Results: Compared with 0 μg/mL HUVEC-EVs, 10, 20 and 40 μg/mL HUVEC-EVs improved the proliferation, plate cloning and migration of MDA-MB-231 and MCF-7 cells significantly (P<0.05); there was no significant difference in total JAK2 and STAT3 protein expression (P>0.05), while the expression of p-JAK2 and p-STAT3 protein increased markedly(P<0.05). Conclusion: HUVEC-EVs may promote breast cancer cell proliferation and migration through the phosphorylation of JAK2/STAT3 signaling pathway. ［Key words］human umbilical vein endothelial cells; extracellular vesicles; breast cancer; JAK2/STAT3 pathway